The treatment of human cancer with chemotherapeutic agents has been long practiced, with varying degrees of success. There remains an acute need to be able to discover agents that can be administered in conjunction with chemotherapeutic agents to increase the effectiveness of the latter.
The peritoneum is the inner lining found throughout the abdominal cavity. Cancer cells can spread into the peritoneum from tumors originally located in the colon, pancreas, appendices, gastrointestinal tract, ovaries, and other organs. Typically, when cancerous cells have spread (metastasized) from one location to another, doctors will prescribe systemic chemotherapeutic compounds by injection into a patient's bloodstream. The goal of such methods is to destroy wayward cancer cells by basically saturating a patient's body with chemical poisons. This is effective for a number of metastatic cancers. However, such methods are far less effective for peritoneal cancers, due to the fact that the abdominal lining naturally has significantly less blood flow than other tissues in the body, thus creating what is known in the art as a “peritoneal barrier”.
Accordingly, the penetration of chemotherapeutic chemicals into the peritoneal cavity is very low. Reacting to this challenge, medical researchers developed a procedure called intraperitoneal hyperthermic chemo-perfusion or “HIPEC”. Immediately following tumor debulking surgery a surgeon can administer the HIPEC procedure by inserting tubing into the abdomen and circulating approximately three liters of sterile solution throughout the abdominal cavity. The solution is heated to approximately 42 C (107.6 F) and then chemotherapeutic agents are added. This heated chemotherapy solution is circulated throughout the abdominal cavity for approximately 90 minutes to 2 hours. After this time period the solution is drained and the abdominal cavity is rinsed.
HIPEC delivers what systemic administration cannot—the direct contact of anti-cancer compounds to the cancerous cells found within the peritoneal area. Researchers discovered that heating the circulating chemotherapy solution further increased their ability to kill cancer cells in the patient's abdomen. The use of HIPEC is expanding, worldwide.
Another procedure, called “IP Therapy”, oftentimes used to treat ovarian cancer, is similar to HIPEC, namely, chemotherapy is delivered directly to tumors confined to the peritoneal cavity through abdominal access ports installed through the skin surface. However, heat is not typically used, and the solution is not circulated but left in the abdominal cavity to be absorbed. This method is used to treat ovarian cancer. Generally, six cycles of chemotherapy solution are administered, once every three weeks.
The current carrier solutions used in the art generally consist of Lactated Ringers (LR)— which is used for HIPEC, IP Therapy, and related therapies. LR is sterile water with trace amounts of sodium chloride, potassium chloride, and calcium chloride. LR is used throughout the hospital for IV electrolyte balancing; its use in HIPEC, IP Therapy, and related therapies is as a carrier for heat and chemotherapy.
Before the present invention is described in greater detail, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.
Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.
Certain ranges are presented herein with numerical values being preceded by the term “about.” The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described.
All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.
It is noted that, as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation.
As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible.